Stress and hippocampal volume in rodents, a longitudinal study

压力对记忆的影响至少部分是由于它对海马体的影响，海马体是大脑中对学习和记忆很重要的区域。虽然慢性应激可使海马体积减小，但海马收缩的功能意义尚不清楚。理解海马萎缩的功能意义的困难部分可能是由于几乎完全使用横断面方法来研究应激和非应激个体之间的海马体积差异。然而，横断面研究未能揭示因果关系。另一个问题是在大多数压力研究中未能控制压力易感性的个体差异。对经历过大规模创伤事件的人的精神病理学调查显示，并非所有人都受到这些事件的相似影响，因此有些人对创伤有弹性。******这个新的NSERC应用程序是建立在一个新兴的长期目标，我的实验室揭示的功能意义和机制的压力诱导海马萎缩。使用非侵入性MRI方法测量压力暴露前后的海马体积，我们发现易受慢性社会失败压力影响的小鼠表现出压力诱导的体积变化。然而，这些变化并没有在那些能够适应长期社会失败的老鼠身上发现。我们的短期目标是使用这种社会失败模型，它允许我们将易受慢性压力影响或有弹性的老鼠分开来测试以下假设：1)有弹性的老鼠对压力诱导的海马萎缩表现出抵抗力；2)慢性应激对分别负责空间记忆和情绪记忆形成的背侧海马和腹侧海马的体积产生相反的影响；3)应激诱导的海马萎缩与树突重组和小胶质细胞增殖有关。******本研究项目的发现不仅可以促进我们对应激诱导海马萎缩的功能意义和机制的理解，而且还可以为纵向研究小鼠大脑结构的变化开辟新的研究途径。这个研究项目补充了我实验室正在进行的关于应激对海马突触功能影响的研究。这个研究项目的培训可以让受训者掌握在老鼠身上使用非侵入性成像方法，这是一种强大的新兴研究技术，可以帮助他们在学术界和工业界发展自己的事业。

The impact of stress on memory is at least partly due to its influences on the hippocampus, a brain region that is important for learning and memory. Although chronic stress could reduce hippocampal volume, the functional significance of hippocampal shrinkage remains unclear. The difficulty of understanding the functional significance of hippocampal shrinkage may be partly caused by the almost exclusive use of a cross-sectional approach to investigate hippocampal volume differences between stressed and non-stressed individuals. Cross-sectional studies however fail to reveal causality. Another problem is related to the failure to control for individual differences in stress susceptibility in most stress studies. Investigating psychopathologies in people that had experienced wide scale traumatic events revealed that not all people are similarly affected by these events, so that some individual were resilient to trauma. ******This new NSERC application is built on an emerging long term objective of my laboratory to reveal the functional significances and mechanisms of stress-induced hippocampal shrinkage. Using a non-invasive MRI approach to measure hippocampal volume before and after stress exposure, we have found that mice that are susceptible to chronic social defeat stress displayed stress-induced volume changes. Nonetheless, these changes were not found in mice that are resilient to chronic social defeat. Our short term objective is to use this social defeat model that allows us to separate mice that are susceptible or resilient to chronic stress to test the following hypotheses: 1) resilient mice exhibit a resistance to stress-induced hippocampal shrinkage; 2) chronic stress exerts opposing effects on the volume of the dorsal and ventral hippocampus, which are responsible for spatial and emotional memory formation, respectively, and 3) stress-induced hippocampal shrinkage is related to dendritic reorganization and microglia proliferation.******Findings from this research program could not only advance our understanding of the functional significance and mechanisms of stress-induced hippocampal shrinkage, but also allow us to develop a new research avenue for longitudinally investigating changes in mouse brain structures. This research program complements the ongoing research of my lab to investigate the impact of stress on hippocampal synaptic function. Training from this research program could equip trainees to use non-invasive imaging approaches on mice, which are powerful but newly emerging research techniques that could help them develop their career in both academia and industry.